DESCRIPTION: (Applicant's Abstract) The goal of this proposal is to examine effects of chronic marijuana use on human brain structure, brain function, and cognition using state-of-the-art methods for combining neuroimaging techniques with cognitive assessments. If some marijuana users develop long term cerebral dysfunction, the potential costs to society in increased health care costs and decreased productivity could be high. Marijuana is the most widely used illicit drug in the U.S.A. Following well over a decade of generally declining use, its popularity has increased markedly among youth in the last 3-4 yr, prompting renewed concerns about its possible health consequences. Drug abuse and neuroimaging researchers will join forces in the proposed research to replicate our earlier findings of cognitive impairments in heavy marijuana users and study marijuana's effects on brain structure and regional cerebral blood flow (rCBF) using magnetic resonance imaging and positron emission tomography (PET), respectively. Cognitive activation tests administered during PET imaging will be selected based on our previous PET work and research on chronic marijuana use, and will emphasize tests of memory and attention. We hypothesize that chronic marijuana users will show impairments in these cognitive functions and reduced rCBF in brain regions that we have previously found to be active during performance of these tests in normal controls. More extensive tests of these types will be administered in a separate session not involving neuroimaging. Marijuana users and non-users will be matched on intellectual function before the onset of drug use, using records of scores on standardized tests that are available for children educated in virtually all parts of Iowa. Similar tests suitable for adults will be administered to subjects to assess their current capabilities. Only a handful of previous studies have examined effects of chronic marijuana use with neuroimaging techniques, and all but one were conducted years ago. Abilities of neuroimaging techniques to detect subtle changes in brain structure and function have improved enormously in recent years. No previous studies of chronic marijuana use have assessed changes in brain function associated with specific cognitive activities. Most previous studies of marijuana's chronic effects on cognition have been methodologically weak, and none except our own previous study observed cognitive impairments in marijuana users relative to controls matched on premorbid intellectual abilities. Thus, when completed, the proposed research will make important additions to existing knowledge concerning effects of chronic marijuana use on human brain structure, brain function, and cognition.